De rol van de slijmvliezen bij het ontstaan van auto-antistoffen in reumatoïde artritis

Rationale: A subset of rheumatoid arthritis (RA) patients harbour antibodies against several post-translational modifications and are frequently positive for rheumatoid factor. The exact pathophysiology of the development of the autoantibody response and of RA remains unknown. Investigations into genetic and environmental risk factors and systemic immune dysregulation have led to the hypothesis that the mucosal surfaces might be involved in the pathogenesis of seropositive RA. It is proposed that tolerance against post-translational modifications is broken at the mucosa, inducing an cascade leading to a systemic inflammatory response and clinical disease.

Objective: We aim to perform an in-depth investigation into the role of the mucosal immune response in the pathogenesis of rheumatoid arthritis. Our objectives are to study the presence of RA-specific autoantibodies and several other biomarkers (cytokines, antigens and microbiome) in mucosal fluids of RA-patients.

Study design: At the rheumatology department of the LUMC a cross-sectional study will be performed in which peripheral blood, feces, saliva and sputum (optional) from patients with rheumatoid arthritis and healthy controls are collected and several clinical (patient) characteristics will be recorded. (Due to the covid-19 pandemic no sputum will be collected at the moment)

Study population: Patients older than 18 years with a definite diagnosis of rheumatoid arthritis according to the ACR/EULAR 2010 criteria, and healthy controls without inflammatory arthritis, are eligible provided that they meet the inclusion criteria and no exclusion criteria.

Main study parameters: The detection of several RA associated antibodies and their distinct antibody features in feces, saliva and sputum of patients. This will be compared to the autoantibody profile in serum. Among the distinct antibody features that will be explored are isotype usage, fine-specificity, glycosylation of Fc- and Fab-region, avidity and affinity.

Nature and extent of the burden and risks associated with participation and benefit: Participant will need to self-collect feces. Saliva is collected by the passive drooling method. Blood sampling will be performed at the central blood draw facility of the LUMC and a questionnaire will be used to collect clinical parameters. If participants give additional consent for sputum donation, sputum induction will take place using a disposable device, the LungFlute®, through which they have to breath out several times. The risks of this study are limited to the collection of peripheral venous blood and sputum. Any symptoms caused by blood sampling or sputum induction are usually mild and symptoms will recover fully and spontaneously. The participants do not benefit from this study, but their participation could lead to improved future therapeutic care for RA patients.

A subset of rheumatoid arthritis (RA) patients harbour antibodies against several post-translational modifications and are frequently positive for rheumatoid factor. The exact pathophysiology of the development of the autoantibody response and of RA remains unknown. Investigations into genetic and environmental risk factors and systemic immune dysregulation have led to the hypothesis that the mucosal surfaces might be involved in the pathogenesis of seropositive RA. It is proposed that tolerance against post-translational modifications is broken at the mucosa, inducing an cascade leading to a systemic inflammatory response and clinical disease. We aim to perform an in-depth investigation into the role of the mucosal immune response in the pathogenesis of rheumatoid arthritis.

1 time point

Participants will donate blood, saliva, sputum (optional) and feces once and will have to fill out an online questionnaire